GRB2 SH3 binding peptides and methods of isolating and using same

Abstract

Peptides having general and specific binding affinities for the Src homology region 3 (SH3) domains of proteins are disclosed in the present invention. In particular, SH3 binding peptides have been isolated from phage-displayed random peptide libraries which had been screened for isolates that bind to bacterial fusion proteins having an SH3 domain and glutathione S-transferase (GST). Preferred peptides are disclosed which comprise a core 7-mer sequence (preferably, a consensus motif) and two or more, preferably at least six, additional amino acid residues flanking the core sequence, for a total length of 9, preferably at least 13, amino acid residues and no more than about 45 amino acid residues. Such peptides manifest preferential binding affinities for certain SH3 domains. The preferred peptides exhibit specific binding affinities for the Src-family of proteins. In vitro and in vivo results are presented which demonstrate the biochemical activity of such peptides.

What is claimed is:  
     
       1. A purified peptide that binds to the N terminal SH3 domain of Grb2, said peptide consisting of an amino acid sequence selected from the group consisting of: 
       KWDSLLPALPPAFTVE (SEQ ID NO: 224),  
       RWDQVLPELPTSKGQI (SEQ ID NO: 225);  
       RFDFPLPTHPNLQKAH (SEQ ID NO: 226);  
       RLDSPLPALPPTVMQN (SEQ ID NO: 227);  
       RWGAPLPPLPEYSWST (SEQ ID NO: 228);  
       YWDMPLPRLPGEEPSL (SEQ ID NO: 229);  
       RFDYNLPDVPLSLGTA (SEQ ID NO: 230);  
       TKKPNAPLPPLPAYMG (SEQ ID NO:231);  
       KWDLDLPPEPMSLGNY (SEQ ID NO: 232);  
       YYQRPLPPLPLSHFES (SEQ ID NO: 234);  
       YYRKPLPNLPRGQTDD (SEQ ID NO: 235);  
       YFDKPLPESPGALMSL (SEQ ID NO: 236);  
       YFSRALPGLPERQEAH (SEQ ID NO: 237);  
       SLWDPLPPIPQSKTSV (SEQ ID NO: 239);  
       SYYDPLPKLPDPGDLG (SEQ ID NO: 240);  
       KLYYPLPPVPFKDTKH (SEQ ID NO: 241); and  
       DPYDALPETPSMKASQ (SEQ ID NO: 242).  
     
     
       2. A composition comprising a peptide of claim  1 , and a sterile carrier.